KEY TAKEAWAYS
- The study aimed to combine specific immune biomarkers from tumors and blood to predict benefits in melanoma treatment.
- Researchers aimed to correlate 31 genes and 40 circulating biomarkers with survival outcomes in ipilimumab vs interferon-treated patients.
- Integrating blood and tumor immune-related biomarkers created a predictive signature for improved prognosis in adjuvant ipilimumab-treated melanoma patients.
In phase III trial E1609 (NCT01274338), ipilimumab showed better results for high-risk melanoma patients compared to interferon-α2b. Patients provided consent approved by IRB at participating institutions. The study aimed to create an improved predictive biomarker signature by merging certain immune markers from tumors and circulating blood based on shared systems immunobiology.
Researchers examined gene expression data from 471 patients treated with ipilimumab and 248 patients treated with interferon, utilizing various techniques, including multicolor flow cytometry and multiplex Luminex. They compared cellular marker expression and serum biomarkers in patient-matched biospecimens collected at baseline, involving 210 ipilimumab-treated and 119 interferon-treated individuals.
Correlations between the expression levels of 31 genes and 40 circulating candidate biomarkers with survival outcomes were assessed. The researchers developed two distinct multivariate Lasso-Cox regression models and an integrative risk prediction model using prioritized biomarkers.
In patient blood samples, specific cell populations linked to immune response, such as CTLA4+Treg and monocytic (M)-MDSC, were associated with poorer overall survival (OS) and recurrence-free survival (RFS). Conversely, an abundance of CXCR3+/CD4+ T cells, CXCR3+/CD8+ T cells, CTLA4+/INFg+/CD8+ T cells, and higher CCL3 and CXCL11 levels were linked to notably improved OS and RFS.
In tumors, certain markers like CXCL9, CD8A, CXCL10, and INPP5D were identified as Tier-1 biomarkers indicating better outcomes, while IDO1, IGKC, and IL2RB were Tier-2 markers also associated with improved outcomes (P<0.05 and P<0.1 respectively).
Researchers devised risk scores based on these prioritized circulating (L-IPI3) and tumor (L-IPI-7) biomarkers to gauge predictive ability. By comparing these risk scores, they found that around 23.4% of patients consistently showed a higher risk, while 29.1% consistently showed a lower risk.
The combined analysis of potential blood and tumor immune-related markers created a foundational profile. This profile enhances the ability to forecast the benefits of immunotherapy in individuals with melanoma, especially when compared to specific biomarker profiles in different body compartments.
The comprehensive profile highlights the importance of having higher levels of tumor-infiltrating and circulating immune cells while maintaining lower levels of immunosuppressive cells. Such conditions in the body suggest a more favorable outlook following adjuvant ipilimumab treatment.
Source: https://jitc.bmj.com/content/11/Suppl_1/A52
Clinical Trial: https://clinicaltrials.gov/study/NCT01274338
Tarhini AA, Obermayer A, Lee SJ, et al45 An integrative immune signature of complementary circulating and tumoral biomarkers maximizes the predictive power of adjuvant immunotherapeutic benefits for high-risk melanomaJournal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.0045.
